Intrathymic Autoantigens and their Role in the Shaping of the Autoimmune T Lymphocyte Repertoire

Abstract

The physical deletion of self-reactive lymphocytes from the immune repertoire is the only way to provide an absolute guarantee for continued maintenance of self tolerance. In fact, deletion of self-reactive T cell clones does occur in the development of the immune repertoire. However, this deletional, self-tolerogenic mechanism is restricted to a limited set of autoantigens, especially those available in the thymus at high concentration. This is not the case for the majority of tissue specific autoantigens, and expression of the autoantigen does not lead to the complete elimination of specific self-reactive T cells. As a consequence all healthy organisms harbor unexpectedly high numbers of self reactive T cells, some of which possess the potential to attack the body’s own tissue and to cause disease.